We are studying the mechanism by which sphingolipids regulate immunity and inflammation. Our focus has been on sphingosine-1-phosphate (S1P), a bioactive lipid enriched in the vascular and lymphatic systems, and the S1P receptors, found on immune cells and the endothelium. Essential roles for S1P and its receptors have been found for immune system development and homeostasis as well as for the regulation of immune responses and inflammation. In collaborative studies, we have found that i) activation of the S1P1 receptor limits expression of pro-inflammatory cytokine in mouse macrophages and ii) endothelial permeability mediated by angiopoietin-1 is regulated by sphingosine kinase 1.